Diagnosis and definition of treatment-resistant depression

Objective: The specifit brain regions involved in the normal emotional states of transient sadness or happiness are poorly understood. The authors therefore sought to determine if H 2 15 O position emission tomography (PET) might demonstrate changes in regional cerebral blood flow (rCBF) associated with transient sadness or happiness in healthy adult women. Method: Eleven healthy and never mentally ill adult women were scanned, by using PET and H 2 15 O, during happy, sad, and neutral states induced by recalling affect-appropriate life events and looking at happy, sad, or neutral human fates. Results: Compared to the neutral condition, transient sadness significantly activated bilateral limbic and paralimbic structures (cingulate, medial prefrontal, and mesial temporal cortex), as well as brainstem, thalamus, and caudate/putamen. In contrast, transient happiness had no areas of signifitantly increased activity but was associated with significant and widespread reductions in cortical rCBF, especially in the right prefrontal and bilateral temporal-parietal regions. Conclusions: Transient sadness and happiness in healthy volunteer women are accompanied by significant changes in regional brain activity in the limbic system, as well as other brain regions. Transient sadness and happiness affect different brain regions in divergent directions and are not merely opposite activity in identical brain regions. These findings have implications for understanding the neural substrates of both normal and pathological emotion

Brain activity during transient sadness and happiness in healthy women.

Background
Assertive Community Treatment (ACT) was developed in the early 1970s as a response to the closing down of psychiatric hospitals. ACT is a team-based approach aiming at keeping ill people in contact with services, reducing hospital admissions and improving outcome, especially social functioning and quality of life.

Objectives
To determine the effectiveness of Assertive Community Treatment (ACT) as an alternative to i. standard community care, ii. traditional hospital-based rehabilitation, and iii. case management. For each of the three comparisons the main outcome indices were i. remaining in contact with the psychiatric services, ii. extent of psychiatric hospital admissions, iii. clinical and social outcome and iv. costs.

Search strategy
Electronic searches of CINAHL (1982-1997), the Cochrane Schizophrenia Group's Register of trials (1997), EMBASE (1980-1997), MEDLINE (1966-1997), PsycLIT (1974-1997) and SCISEARCH (1997) were undertaken. References of all identified studies were searched for further trial citations.

Selection criteria
The inclusion criteria were that studies should i. be randomised controlled trials, ii. have compared ACT to standard community care, hospital-based rehabilitation, or case management and iii. have been carried out on people with severe mental disorder the majority of whom were aged from 18 to 65. Studies of ACT were defined as those in which the investigators described the intervention as "Assertive Community Treatment" or one of its synonyms. Studies of ACT as an alternative to hospital admission, hospital diversion programmes, for those in crisis, were excluded. The reliability of the inclusion criteria were evaluated.

Data collection and analysis
Three types of outcome data were available: i. categorical data, ii. numerical data based on counts of real life events (count data) and iii. numerical data collected by standardised instruments (scale data). Categorical data were extracted twice and then cross-checked. Peto Odds Ratios and the number needed to treat (NNT) were calculated. Numerical count data were extracted twice and cross-checked. Count data could not be combined across studies for technical reasons (the data were skewed) but all relevant observations based on count data were reported in the review. Numerical scale data were subject to a quality assessment. The validity of the quality assessment was itself assessed. Numerical scale data of suitable quality were combined using the standardised mean difference statistic where possible, otherwise the data were reported in the text or 'Other data tables' of the review.

Main results
ACT versus standard community care 
Those receiving ACT were more likely to remain in contact with services than people receiving standard community care (OR 0.51, 99%CI 0.37-0.70). People allocated to ACT were less likely to be admitted to hospital than those receiving standard community care (OR 0.59, 99%CI 0.41-0.85) and spent less time in hospital. In terms of clinical and social outcome, significant and robust differences between ACT and standard community care were found on i. accommodation status, ii. employment and iii. patient satisfaction. There were no differences between ACT and control treatments on mental state or social functioning. ACT invariably reduced the cost of hospital care, but did not have a clear cut advantage over standard care when other costs were taken into account.

ACT versus hospital-based rehabilitation services 
Those receiving ACT were no more likely to remain in contact with services than those receiving hospital-based rehabilitation, but confidence intervals for the odds ratio were wide. People getting ACT were significantly less likely to be admitted to hospital than those receiving hospital-based rehabilitation (OR 0.2, 99%CI 0.09-0.46) and spent less time in hospital. Those allocated to ACT were significantly more likely to be living independently (OR (for not living independently) 0.19, 99%CI 0.06-0.54), but there were no other significant and robust differences in clinical or social outcome. There was insufficient data on costs to permit comparison.

ACT versus case management 
There were no data on numbers remaining in contact with the psychiatric services or on numbers admitted to hospital. People allocated to ACT consistently spent fewer days in hospital than those given case management. There was insufficient data to permit robust comparisons of clinical or social outcome. The cost of hospital care was consistently less for those allocated to ACT, but ACT did not have a clear cut advantage over case management when other costs were taken into account.

Authors' conclusions
ACT is a clinically effective approach to managing the care of severely mentally ill people in the community. ACT, if correctly targeted on high users of in-patient care, can substantially reduce the costs of hospital care whilst improving outcome and patient satisfaction. Policy makers, clinicians, and consumers should support the setting up of ACT teams.

Assertive community treatment for people with severe mental disorders

Background People who are prescribed self-administered medications typically take less than half the prescribed doses. Efforts to assist patients with adherence to medications might improve the benefits of prescribed medications, but also might increase their adverse effects. Objectives To update a review summarizing the results of randomized controlled trials (RCTs) of interventions to help patients follow prescriptions for medications for medical problems, including mental disorders but not addictions. Search strategy Computerized searches were updated to September 2004 without language restriction in MEDLINE, EMBASE, CINAHL, The Cochrane Library, International Pharmaceutical Abstracts (IPA), PsycINFO and SOCIOFILE. We also reviewed bibliographies in articles on patient adherence and articles in our personal collections, and contacted authors of original and review articles on the topic. Selection criteria Articles were selected if they reported an unconfounded RCT of an intervention to improve adherence with prescribed medications, measuring both medication adherence and treatment outcome, with at least 80% follow-up of each group studied and, for long-term treatments, at least six months follow-up for studies with positive initial findings. Data collection and analysis Study design features, interventions and controls, and results were extracted by one reviewer and confirmed by at least one other reviewer. We extracted adherence rates and their measures of variance for all methods of measuring adherence in each study, and all outcome rates and their measures of variance for each study group, as well as levels of statistical significance for differences between study groups, consulting authors and verifying or correcting analyses as needed. Main results For short-term treatments, four of nine interventions reported in eight RCTs showed an effect on both adherence and at least one clinical outcome, while one intervention reported in one RCT significantly improved patient compliance, but did not enhance the clinical outcome. For long-term treatments, 26 of 58 interventions reported in 49 RCTs were associated with improvements in adherence, but only 18 interventions led to improvement in at least one treatment outcome. Almost all of the interventions that were effective for long-term care were complex, including combinations of more convenient care, information, reminders, self-monitoring, reinforcement, counseling, family therapy, psychological therapy, crisis intervention, manual telephone follow-up, and supportive care. Even the most effective interventions did not lead to large improvements in adherence and treatment outcomes. Six studies showed that telling patients about adverse effects of treatment did not affect their adherence. Authors' conclusions Improving short-term adherence is relatively successful with a variety of simple interventions. Current methods of improving adherence for chronic health problems are mostly complex and not very effective, so that the full benefits of treatment cannot be realized. High priority should be given to fundamental and applied research concerning innovations to assist patients to follow medication prescriptions for long-term medical disorders.

Interventions to enhance medication adherence.

Objective: The authors’ objective was to compare the urinary cortisol excretion of Holocaust survivors with posttraumatic stress disorder (PTSD) (N=22) to that ofHolocaust survivors without PTSD (N=25) and comparison subjects not exposed to the Holocaust (N=15). Method: Twenty-four-hour urine samples were collected, and the following day, subjects were evaluated for the presence and severity ofpast and current PTSD and other psychiatric conditions. Results: Holocaust survivors with PTSD showed significantly lower mean 24-hour urinary cortisol excretion than the two groups ofsubjects without PTSD. Multiple correlation analysis revealed a significant relationship between cortisol levels and severity of PTSD that was due to a substantial association with scores on the avoidance subscale. Conclusions: The present findings replicate the authors’ previous observation oflow urinary cortisol excretion in combat veterans with PTSD and extend these findings to a non-treatment-seeking civilian group. The results also demonstrate that low cortisol levels are associated with PTSD symptoms ofa clinically significant nature, rather than occurring as a result ofexposure to trauma per se, and that low cortisollevels may persist for decades following exposure to trauma among individuals with chronic PTSD. (AmJ Psychiatry 1995; 152:982-986)

Low Urinary Cortisol Excretion in Holocaust Survivors With Posttraumatic Stress Disorder

148th Annual Meeting of the American Psychiatric Association

/pdf/6th-international-conference-on-the-reduction-of-drug-4bp3giysi6.pdf

6th International Conference on the Reduction of Drug-Related Harm

Objective Vaccine efficacy among previously exposed, but currently uninfected women, i.e., those who have serological evidence of a prior human papillomavirus (HPV) infection without corresponding detectable HPV DNA, remains incompletely defined. This meta-analysis assessed the serotype-specific efficacy of prophylactic HPV vaccination against HPV16/18 persistent infection (PI) and cervical intraepithelial neoplasia (CIN) among seropositive, DNA negative (SPDN) women enrolled to randomized controlled trials (RCTs) of HPV L1-based vaccines. Methods Searches were conducted on 08/16/20 on MEDLINE, Embase, Scopus and CENTRAL. RCTs of L1-based prophylactic bivalent or quadrivalent HPV vaccines, reporting serotype-specific clinical efficacy endpoints in the HPV16/18 seropositive, DNA-negative populations were included. Relative risks (RRs) of 6-month PI (6mPI), 12-month PI (12mPI), CIN1+ and CIN2+ were pooled using a random-effects model. Results A total of 1,727 citations were reviewed. 8 studies, with a total of 9,569 SPDN participants, met all eligibility criteria. The RR of 6mPI (RR=0.22; 95% confidence interval [CI]=0.08–0.61; p=0.018), 12mPI (RR=0.20; 95% CI=0.05–0.80; p=0.035), CIN1+ (RR=0.13; 95% CI=0.05–0.30; p=0.003) and CIN2+ (RR=0.15; 95% CI=0.04–0.59; p=0.022) was significantly reduced in the vaccinated compared to the unvaccinated group. Conclusion Our findings suggest high serotype-specific efficacy for HPV vaccination among cohorts of women with evidence of prior HPV16/18 infections, including 87% efficacy (95% CI=70%–95%; p=0.003) against HPV16/18 cervical dysplasia. HPV vaccination is highly effective among uninfected women, regardless of prior exposure history. Trial Registration PROSPERO Identifier: CRD42020206888

HPV vaccination among seropositive, DNA negative cohorts: a systematic review & meta-analysis

e22544 Background: Lynch syndrome is the most common hereditary cause of colorectal and endometrial cancer. Non-genetic risk factors, including obesity, physical activity, alcohol intake, and smoking are well-established in sporadic cancers but are less studied in Lynch syndrome. A better understanding of these risk factors could directly contribute to cancer prevention. Methods: Searches were conducted on MEDLINE, Embase and Web of Science for retrospective or prospective cohort studies that investigated the association between modifiable risk factors and the risk of colorectal or endometrial cancer in people with Lynch syndrome. Screening, data extraction and quality assessment were completed by 2 reviewers independently. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) for colorectal and endometrial cancer were pooled using a random effects model. The protocol was prospectively registered on PROSPERO (CRD 42022378462) and the meta-analysis conducted in accordance with PRISMA and MOOSE reporting guidelines. Results: A total of 770 citations were reviewed. Twelve cohort studies involving 12685 patients with Lynch syndrome investigated risk of colorectal cancer, while 3 studies including 1865 patients assessed risk factors for endometrial cancer. Eight colorectal cancer studies were eligible for meta-analysis. Obesity (HR 2.38, 95% CI 1.52-3.73) and alcohol intake (HR 1.43, 95% CI 1.05-1.94) increased colorectal cancer risk, physical activity was protective (HR 0.66, 95% CI 0.52-0.83), and smoking had no effect (HR 1.02 95% CI 0.83-1.27). Type 2 diabetes mellitus and low dietary intake of calcium and multivitamins might increase risk of colorectal cancer, although more studies are needed. There is a paucity of data pertaining to endometrial cancer. In a qualitative synthesis of 3 endometrial cancer cohort studies, female hormonal risk factors and type 2 diabetes mellitus may affect the risk of endometrial cancer, but obesity was not associated with an increased risk. Conclusions: Lifestyle recommendations related to weight, physical activity, and alcohol may also be relevant to cancer prevention for individuals with Lynch syndrome and may provide a meaningful adjunct to standard interventions for risk modification. There are very poor data examining modifiable risk factors in endometrial cancer. Further high-quality prospective cohort studies, in particular including endometrial cancer as an endpoint, are needed to inform evidence-based cancer prevention strategies in this high-risk population.

Modifiable risk factors and risk of colorectal and endometrial cancer in Lynch syndrome: A systematic review and meta-analysis.

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148th Annual Meeting of the American Psychiatric Association

6th International Conference on the Reduction of Drug-Related Harm

HPV vaccination among seropositive, DNA negative cohorts: a systematic review & meta-analysis

Modifiable risk factors and risk of colorectal and endometrial cancer in Lynch syndrome: A systematic review and meta-analysis.